Evidence suggesting that prostaglandins are physiologically and biochemically active in skin is rapidly accumulating (1-3). Recent reports (4-6) have implicated this class of compounds as potent mediators of inflammatory reactions. Also, the addition of PGE1 and PGB1 to organ cultures of skin stimulated the proliferation and keratinization of the epidermis (7). We have used two model systems to evaluate the possible involvement of PGE2 in the process of epidermal maturation and keratinization: 1) Rats fed a diet deficient in essential fatty acids (EFA) developed characteristic scaly dermatosis that responded to topical application of PGE2 but not to vehicle (propylene glycol:ethanol, 3:7), corticosteroids or methotrexate. These results suggest that a significant relationship exists between EFA, PGE2 and scaly skin disease. 2) Using an in vitro system for the study of lipogenesis by skin, PGE2 was found to inhibit the synthesis of sterol esters from radioactive precursors. These sterol esters have been associated with the keratinization process again indicating the possible importance of PGE2 in skin homeostasis. We therefore propose to extend these studies: (a) To examine the enzymatic controls in prostaglandin biosynthesis, including the effects of inhibitors and prostaglandin antagonists on the enzyme system. (b) To examine in detail the factors which provoke the release of fatty acid precursors from phospholipids for prostaglandin synthesis and their controls. (c) To elucidate the mechanism of action of PGE2 on the enzymes involved with the synthesis and hydrolysis of sterol esters. (d) To develop a sensitive assay for measuring prostaglandins in skin. (e) Extending our studies to include scaling dermatoses such as psoriasis.